Birt-Hogg-Dube Syndrome

What causes BHD

The FLCN gene makes a protein called folliculin, which acts as a tumor suppressor, helping control cell growth. People with BHD inherit one faulty copy. When the second copy is damaged in a cell, that cell can grow abnormally, forming skin bumps, lung cysts or kidney tumors.

BHD is autosomal dominant: each child of an affected parent has a 50% chance of inheriting it. Severity varies widely, even within one family. Some people have only lung cysts, others only skin bumps.

Skin features

• Fibrofolliculomas: benign tumors of hair follicles that appear as small (2 to 4 mm), smooth, pale or skin-colored, dome-shaped bumps on the face (especially the nose and cheeks), neck and upper trunk.
• Trichodiscomas and acrochordons (skin tags) are also common.
• Bumps usually appear after age 20 and increase with age.
• They are harmless and do not become cancerous.

Lung features

• Most adults with BHD have multiple thin-walled cysts in the lower and inner parts of the lungs on CT scans.
• Lung function is usually normal.
• The cysts can rupture and cause a pneumothorax (collapsed lung). People with BHD have a much higher risk than the general population, and collapses tend to recur.
• Symptoms of pneumothorax: sudden one-sided chest pain, breathlessness and sometimes a fast heartbeat.

BHD is an important cause of apparently "spontaneous" pneumothorax, and its lung cysts can resemble those of lymphangioleiomyomatosis, particularly when there is a family history.

Kidney features

• People with BHD have a raised risk of kidney tumors, estimated at roughly 1 in 4 to 1 in 3 over a lifetime in many studies.
• Tumors are often multiple and in both kidneys.
• The most common types are hybrid oncocytic tumors and chromophobe renal cell carcinoma, which tend to grow slowly. Clear cell kidney cancer, which can be more aggressive, also occurs.
• Kidney tumors usually cause no symptoms until they are large, which is why screening matters.

Diagnosis

• Genetic testing for FLCN variants confirms the diagnosis.
• Skin biopsy of a bump can show fibrofolliculoma.
• Chest CT shows typical lung cysts.
• Kidney MRI detects tumors.

Clinical criteria include multiple fibrofolliculomas, typical lung cysts or pneumothorax, early-onset or multiple chromophobe or hybrid kidney tumors, and a family history. Relatives of an affected person can have predictive genetic testing after genetic counseling.

Management

Kidney surveillance

• MRI of the kidneys every 1 to 3 years from about age 20, as recommended by expert guidelines. MRI is preferred because it avoids repeated radiation.
• Small tumors are monitored. Tumors that reach about 3 cm are usually removed by nephron-sparing surgery (removing only the tumor), because people with BHD may need further surgery in the future.

Lungs

• Pneumothorax is treated in the usual way: observation, needle aspiration or a chest drain.
• After a first collapse, many specialists recommend pleurodesis (a procedure to stick the lung to the chest wall) to prevent recurrence.
• Avoid smoking, which damages the lungs further.
• Discuss scuba diving and flying with a doctor; diving is generally discouraged because of pressure changes. Air travel is usually fine unless you have a current pneumothorax or symptoms.

Skin

The bumps are harmless. For cosmetic reasons they can be treated with laser ablation, electrosurgery, shave removal or curettage, though they often return.

Outlook

Life expectancy is generally normal when kidney tumors are detected early through regular screening. Pneumothorax can be distressing and recurrent but is manageable. Knowing the diagnosis allows family members to be tested and screened.

Frequently asked questions

What is Birt-Hogg-Dube syndrome?

It is a rare inherited condition caused by changes in the FLCN gene. It causes harmless skin bumps on the face and neck, lung cysts that can lead to a collapsed lung, and an increased risk of kidney tumors. It is passed down in families in a dominant pattern.

What are the first signs of BHD syndrome?

Often the first sign is a collapsed lung in a young adult without obvious cause, or small pale bumps on the face and neck appearing in the 20s or 30s. Some people are diagnosed only after a kidney tumor is found or a relative is diagnosed.

Does Birt-Hogg-Dube syndrome cause cancer?

It increases the risk of kidney tumors, some of which are cancerous, such as chromophobe renal cell carcinoma. The skin bumps and lung cysts are not cancerous. Regular kidney MRI scans help find tumors early, when they can be removed safely.

How is BHD inherited?

BHD is autosomal dominant, so each child of an affected parent has a 1 in 2 chance of inheriting the gene change. Genetic counseling and testing can identify which family members carry it and need screening.

How often should people with BHD have kidney scans?

Guidelines generally recommend kidney MRI every 1 to 3 years starting around age 20, more often if a tumor is being monitored. Your specialist will tailor the schedule to your findings and family history.